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According to both trial and clinical data on direct oral anticoagulants (DOACs) elderly patients are at greatest risk of bleeding. It is unclear whether age intrinsically affects anticoagulation response. To investigate the age-related sensitivity to DOACs, we compared the pharmacological activity of the direct factor Xa inhibitor, rivaroxaban, between young and elderly subjects ex-vivo. 36 fit elderly and 30 fit young subjects [median (IQR) age: 83(75–87) vs 30(26–38) years] provided a blood sample. Clotting parameters were measured in the resultant plasma samples incubated with rivaroxaban (100–500 ng/ml). Parametric, non-parametric tests and regression lines adjusted for rivaroxaban concentration and baseline values were used to compare data. Rivaroxaban produced a greater prolongation of both Prothrombin Time (PT) and modified Prothrombin Time (mPT) (both p < 0.001) in the elderly compared to young subjects (with difference in mean PT increasing from 1.6 to 6.1s and for mPT from 23.5 to 71.1s at 100 ng/ml and 500 ng/ml plasma rivaroxaban concentration, respectively). Factor X and factor II activity was significantly lower in the elderly in the presence of rivaroxaban (p < 0.001 for both). Rivaroxaban prolonged time-based parameters and suppressed the amount of thrombin generation to a significantly greater extent in the elderly compared to young subjects [%change from baseline for Endogenous Thrombin Potential (ETP): − 35.0 ± 4.4 vs − 29.8 ± 7.4 nM*min; p = 0.002]. The use of validated DOAC assays will be of considerable benefit for monitoring elderly patients who, because of their increased sensitivity to rivaroxaban, may require lower doses of the drug for therapeutic anticoagulation.

The viruses of the family Coronaviridae are ubiquitous in nature due to their existence in a wide spectrum of mammals and avian species. The coronaviruses, as RNA viruses, exist as quasispecies because of their high rate of mutations. This review elaborates on the pathogenesis and the developed vaccines of most of the ubiquitous coronavirus' diseases, mainly bovine, dromedary camel, porcine, feline, canine, and avian coronaviruses. The review emphasizes the significant setbacks in the full exploitation of most of the pathogenesis of the coronavirus' diseases, raising the prospect of effective vaccines for these diseases. The therapeutical trials for the treatment of SARS-CoV2 and the setbacks of these trials are also addressed. The review draws attention to the lessons accumulated from the large number of studies of the pathogenesis of animals and birds' coronaviruses and their vaccines, particularly the bovine, feline, and avian coronaviruses. The lessons drawn from the studies will have an immense influence on how the human coronaviruses pathogenesis and vaccine development will proceed. In addition, the extensive efforts to designate suitable animal models to study the lately emerged human coronaviruses are one of the invaluable contributions carried out by veterinarian scientists. Finally, factors and determinants that contribute to the possibility of emerging new coronavirus zoonotic disease are elaborated on and a call goes out to urge transdisciplinary collaboration in the implementation of the “One Health” concept.

BackgroundDifferent levels of evidence related to the variable responses of individuals to drug treatment have been reported in various pharmacogenomic (PGx) databases. Identification of gene-drug pairs with strong association evidence can be helpful in prioritizing the implementation of PGx guidelines and focusing on a gene panel. This study aimed to determine the pharmacogenes with the highest evidence-based association and to indicate their involvement in drug-gene interactions.MethodologyThe publicly available datasets CPIC, DPWG, and PharmGKB were selected to determine the pharmacogenes with the highest drug outcome associations. The upper two levels of evidence rated by the three scoring methods were specified (levels A–B in CPIC, 3–4 in DPWG, or 1–2 levels in PharmGKB). The identified pharmacogenes were further ranked in this study based on the number of medications they interacted with.ResultsFifty pharmacogenes, with high to moderately high evidence of associations with drug response alterations, with potential influence on the therapeutic and/or toxicity outcomes of 152 drugs were identified. CYP2D6, CYP2C9, CYP2C19, G6PD, HLA-B, SLCO1B1, CACNA1S, RYR1, MT-RNR1, and IFNL4 are the top 10 pharmacogenes, where each is predicted to impact patients' responses to ≥5 drugs.ConclusionThis study identified the most important pharmacogenes based on the highest-ranked association evidence and their frequency of involvement in affecting multiple drugs. The obtained data is useful for customizing a gene panel for PGx testing. Identifying the strength of scientific evidence supporting drug-gene interactions aids drug prescribers in making the best clinical decision.

Guillain–Barré syndrome is a clinical syndrome manifesting as immune-mediated polyneuropathy. Approximately one-third of affected patients develop respiratory failure, necessitating intensive care unit admission and invasive mechanical ventilation. Multiple factors present at the onset and during intensive care unit stay are established predictors of the requirement for invasive mechanical ventilation. These include the rapid progression of motor weakness, concurrent involvement of peripheral limb and axial muscles, ineffective cough, bulbar muscle weakness, and the decline in rapid vital capacity. However, no reliable criteria currently exist to predict the duration of muscle weakness progression and plateau phases or the time to recovery. We herein report a case of a 55-year-old male admitted to the intensive care unit following a 5-day history of progressive ascending generalized weakness. His condition progressed to quadriplegia, diaphragmatic paralysis, and autonomic dysfunction. A diagnosis of Guillain–Barré syndrome–acute motor axonal neuropathy variant was confirmed via neurological examination, imaging, cerebrospinal fluid analysis, and nerve conduction studies. The patient exhibited no clinical improvement following two courses of five sessions each of plasma exchange and intravenous immunoglobulin. Owing to the refractory nature of his condition, he required more than 5 months of step-down intensive care unit care prior to transfer to a general medical ward and subsequent discharge home on hospital day 182.

Background The quality of food preparation is considered a public health concern. The present study aimed to evaluate the microbiological quality of grilled food and hummus. Materials and methods The study was conducted in Al-Ahsa Governorate, Saudi Arabia. Restaurants were categorized into traditional and non-traditional. Grilled food (meat and chicken) and hummus were collected without prior arrangement with the restaurant staff. All samples were examined for the total aerobic count and the presence of Escherichia coli , Klebsiella pneumoniae , Staphylococcus aureus and Salmonella spp. Staphylococcal enterotoxin and serotypes, antimicrobial susceptibilities and the PCR detection of virulence genes of E. coli and Salmonella spp. were determined. The culture of hands of food handlers was performed by direct swabbing. Results A total of 83 samples, including food and hand swabs, were collected from six traditional and four non-traditional restaurants. All samples cultured yielded acceptable total aerobic count. Of the 83 samples, 36 (43%) tested positive for the targeted organisms. Among these, 38% were hand swabs, 25% were hummus, 19% were meat tikka, and 6% each were meat kebab, chicken tikka, and chicken kebab. In total, E. coli, K. pneumoniae, Salmonella spp. , and S. aureus were cultured from 29, 10, 20, to 13% of the collected samples, respectively. All S. aureus isolates (11) were positive for enterotoxin. E. coli isolates (24) were enteropathogenic with different serotypes, and the stx1, stx2 and eaeA genes were detected. Ten Salmonella isolates with different serotypes were positive for invA gene , and most also harboured hilA and fimH genes. Thirty seven percent of hands grew at least one of the targeted organisms, including one Salmonella . Methicillin-resistant S. aureus (MRSA) was isolated from the hand of a food handler, and ciprofloxacin resistance was detected in 30% of the Salmonella spp. tested. Conclusion We found that food served in local restaurants contained potential pathogens or toxin. Random inspection, including bacterial cultures, and more rigorous rules may be required to improve food production standards. Clinical trial number Not applicable.

Thyroid storm is a rare but life-threatening complication of hyperthyroidism that requires urgent management. While propylthiouracil (PTU) is a key treatment, it carries multiple risks, including potentially fatal risk of agranulocytosis. We report a 40-year-old female with Graves' disease who presented with thyroid storm and compressive goiter. High-dose PTU (1 g loading dose followed by 200 mg every 4 hours) was initiated; however, severe neutropenia (ANC: 0.22×10ˆ3/µL) developed within 48 hours, necessitating immediate drug discontinuation. Bridging therapy with hydrocortisone, cholestyramine, Lugol's solution, was implemented once available, and low-dose carbimazole was cautiously reintroduced under close monitoring without recurrence of neutropenia. Once a euthyroid state was achieved, definitive management with a total thyroidectomy was performed without complications. This case highlights three key learning points: (1) agranulocytosis can occur very early during high-dose PTU therapy; (2) careful bridging strategies are essential to prevent rebound thyroid storm after antithyroid drug withdrawal; and (3) timely transition to definitive surgical management can be lifesaving when antithyroid drug intolerance occurs.

Biomarkers to identify ICU COVID-19 patients at high risk for mortality are urgently needed for therapeutic care and management. Here we found plasma levels of the glycolysis byproduct methylglyoxal (MG) were 4.4-fold higher in ICU patients upon admission that later died (n = 33), and 1.7-fold higher in ICU patients that survived (n = 32),compared to uninfected controls (n = 30). The increased MG in patients that died correlated inversely with the levels of the MG-degrading enzyme glyoxalase-1 ( r 2  = − 0.50), and its co-factor glutathione ( r 2  = − 0.63), and positively with monocytes ( r 2  = 0.29). The inflammation markers, SSAO ( r 2  = 0.52), TNF-α ( r 2  = 0.41), IL-1β ( r 2  = 0.25), CRP ( r 2  = 0.26) also correlated positively with MG. Logistic regression analysis provides evidence of a significant relationship between the elevated MG upon admission into ICU and death (P < 0.0001), with 42% of the death variability explained. From these data we conclude that elevated plasma MG on admission is a novel independent biomarker that predicts mortality in ICU COVID-19 patients.

Vancomycin is commonly prescribed in treatment of methicillin-resistant Staphylococcus aureus infections. While, vancomycins' pharmacokinetic vary among older patients, there is a paucity of data regarding specific characteristics influencing pharmacokinetics in Saudi adult patients. This study aims to establish a population-pharmacokinetic (Pop-PK) model for vancomycin in patients admitted to medical wards, with the focus on identification of patient characteristics influencing vancomycin trough concentrations. A multicenter retrospective study was conducted involving patients aged ≥40 years admitted to medical wards in the Eastern Province, Saudi Arabia and initiated on vancomycin, between January to December 2022. Non-linear mixed-effects modelling (Monolix) was employed to develop the Pop-PK model. A base model was selected based on the Akaike information criterion. Covariates considered included age, sex, body weight, C-reactive protein (CRP), serum creatinine, creatinine clearance (CrCl), and albumin levels. A -value of <0.05 was considered statistically significant for inclusion of covariates in the final model by stepwise addition. The simulation performance of the model was assessed by visual predictive check plot. The final model was simulated using Simulx software to assess the effect of the included covariates on vancomycin trough concentration. A total of 172 vancomycin trough concentrations from 124 patients were analyzed. The final Pop-PK model characterized vancomycin trough concentrations was one compartment distribution with linear elimination. CrCl and CRP were the only covariates included in the final model, as they reduced the between-subject variability (BSV) for clearance (from 173% to 81%). The simulated model demonstrated that high CRP value and low CrCl contributed to increased vancomycin trough concentrations. This study highlights large BSV in trough concentrations among patients and emphasizes the influencing of CrCl and CRP on vancomycin pharmacokinetics in medical care settings.

Non-traumatic fat embolism syndrome (FES) in sickle cell disease (SCD) is associated with high morbidity and mortality. This severe complication arises from bone marrow necrosis, which subsequently can lead to fat embolism syndrome and multi-organ failure. A key challenge in diagnosing and managing this syndrome lies in the absence of established diagnostic criteria and the variability of its clinical presentation. Instant red cell exchange transfusion could be lifesaving once the syndrome is suspected, and the use of therapeutic plasma exchange, as suggested in the literature, can improve outcomes. Here, we report two cases of SCD with FES that were managed successfully with blood transfusion and plasma exchange. Both of them rapidly deteriorated and required intensive care unit admission, where they received red cell exchange followed by plasma exchange. They both made a good recovery and were discharged from the hospital within two weeks.

Sickle cell disease (SCD) is a severe inherited blood disorder characterized by abnormal hemoglobin (HbS) that leads to varying degrees of severity, including chronic hemolysis, episodic vaso-occlusion, and damage to multiple organs, causing significant morbidity and mortality. While SCD is a monogenic disease, its complications are influenced by polygenic factors. SCD prevalence is notably high in regions including the Middle East, with Saudi Arabia reporting significant cases, particularly in the Eastern Province. Most genetic factors associated with SCD outcomes have been identified in populations predominantly from Africa or of African ancestry. This study aims to identify genetic variants that characterize Saudi SCD patients with the potential to influence disease outcomes in this population. A multicenter case-control genome-wide association study (GWAS) was conducted involving 350 adult Saudi SCD patients and 202 healthy controls. Participants were genotyped using the Affymetrix Axiom array, covering 683,030 markers. Rigorous quality control measures were applied to ensure data integrity. Fisher’s exact was used to identify genetic variants with a significant difference in allele frequency (p < 5 × 10−8). Functional annotations and regulatory functions of variants were determined using the Ensembl Variant Effect Predictor (VEP) and RegulomeDB databases. The GWAS identified numerous significant genetic variants characterizing SCD cases in the Saudi population. These variants, distributed across multiple chromosomes, were found in genes with known functional consequences. A substantial proportion of the markers were detected in the olfactory receptor cluster, TRIM family, and HBB locus genes. Many of the identified genes were reported in previous studies showing significant associations with various SCD outcomes, including hemoglobin regulation, inflammation, immune response, and vascular function. The findings highlight the genetic complexity underlying SCD and its clinical manifestations. The identified variants suggest potential molecular biomarkers and therapeutic targets, enhancing our understanding of the molecular basis of SCD in the Saudi population. This is the first genetic analysis characterizing SCD patients compared to healthy individuals, uncovering genetic markers that could serve as diagnostic biomarkers and therapeutic targets. Given the known molecular mechanisms of the detected genetic loci, these provide a foundation for precision medicine in SCD management, highlighting the need for further studies to validate these results and explore their clinical implications.